LUNG CANCER-ANATOMY TO PATHOLOGICAL CLASSIFICATION

BY DR.AYUSH GARG

PG JR-IRADIOTHERAPY

INTRODUCTION• Tobacco consumption is the primary cause of lung cancer.

• Voluntary or involuntary cigarette exposure accounts for 80% to 90% of all cases of Lung cancer.

• Indoor Radon exposure is now the 2nd cause of Lung cancer in USA

• Other known risk factors are-• Occupationl and environmental carcinogens-• Asbestos• Arsenic and• Plycyclic Hydrocarbons

EPIDEMIOLOGY In the world lung cancer accounts for 13% of total cases and 18% cancer

related deaths.

Lung cancer is the second most common cancer and most common cause of cancer related death among American men and women.

Lung cancer is rare below age 40, with rates increasing until age 80, after which the rate tapers off.

Overall 5 years survival rate is approx 16%.

The projected lifetime probability of developing lung cancer is estimated to be • approximately 8% among males and • approximately 6% among females.

• The incidence and mortality rates for men began to drop around 1990 and latest analysis suggests first time drop in women also.

• The lag in the trend of lung cancer rates in women compared with men reflects historical differences in cigarette smoking between the sexes.

• Cigarette smoking in women peaked about 20 years later than in men.

Demographic data of lung cancer from Indian studies.

S. No Details 1986-2001 2001-2011

1. Total cases 173500 2973002. M:F 6.67:1 5.76:1

3. Mean age (yrs) 52.16 54.6

4. Urban: Rural 19.6 - 81.6 18.4 - 80.4

5. Occupation FarmersLabourers Clerks/teachers BusinessmenHousewivesOthers

13.9 - 48%21.0 - 27.3%16.7%21.3%8.0 - 14.7%23%

6. Religion Hindus MuslimsChristians

75.1%18.9%5.9%

:IACM Journal April-June 2012

Histology (NCDB 2000-2010)Non Small Cell 85% Adenocarcinoma 37% Squamous 25%

NSCL 19%

Other 12% Large Cell 4% Bronchoalveolar 3%Small Cell 15%

non small cell small cell

RISK FACTORSMajority (80–90%) by cigarette smoking.

-Cigarette smokers have a 10 fold or greater increase in risk.

-One genetic mutation is induced for every 15 cigarettes smoked.

- Cigarette smoking increases the risk of all the major lung cancer cell types.

- Environmental tobacco smoke (ETS) or second hand smoke is also an established cause of lung cancer.

• In Indian patients with lung cancer, history of active tobacco smoking was found in 87% of males and 85% of females.

• History of passive tobacco exposure is found in 3% in India. So 90% of all cases in India resulted from tobacco exposure.

Prior lung diseases such as -chronic bronchitis, -emphysema, and - tuberculosis

Air pollution:

• 5 year survival for lung cancer has gone from 12 to 17% in 2008.

• Most people are diagnosed in advance stages: Local (15%), Regional (22%), Distant (56%)

• Cure rate stage is poor: Local (52%), Regional (25%), Distant (4%)

Risk of getting lung CancerSmoking Men Women

Non-smoker 0.2% 0.4%

Quit 5.5% 2.6%

Current 15.9% 9.5%

Heavy 24.4% 18.5%

European study in 2006, defined heavy as > 5 cigarettes per day

Effect of Smoking Reduction on Lung Cancer RiskNina S. Godtfredsen; Eva Prescott; Merete Osler JAMA. 2005;294:1505-1510.

Occupational risk of lung cancer: S.No Occupational

carcinogensRisk

1. Asbestos Insulation and shipyard workers,increase in risk of lung cancer after 10 years of exposure, with concurrent smoking increases risk 90 fold.

2. Arsenic Smelters and vineyard workers,Upper lobe predominance.

3. Nickel Squamous cell carcinoma-MC

4. Radiation Uranium mining, Oat cell carcinoma -MC

5. Haematite mining Due to radon exposure

6. Hard rock mining Chromium exposure,Squamous cell- MC

7. Chloromethyl Oat cell -MC

8. Ethers and mustard gas Squamous and undifferentiated -MC

9. Soots , Tars Coke oven workers

10 Oils and cokes Gas house workers, roofers

ANATOMY

Fissures & Lobes of the Right Lung

Right Upper Lobe

Right Middle Lobe

Right lower Lobe

Fissure of the Left Lung

Left Upper Lobe

Left Lower Lobe

Segmental Bronchi

Parts of Lung• Conical in shape• • Each lung has an apex,base,3 borders and 2 surfaces.

• Surfaces-

• Costal surface- broad and pressed against the rib cage.

• Mediastinal surface- smaller, concave and faces medially.

• Apex[apex pulmonis]-rounded & extends to the root of the neck[2.5-4cm above the level of sternal end of first rib]

• The base[basis pulmonis]- is broad, concave & rest on the convex surface of diaphragm.

• Borders-1. Inferior border- separates the base from the costal surface .

2. Posterior border- is broad & rounded& is received into the deep concavity on either side of the vertebral column.

3. Anterior border- thin& sharp, and overlaps the front of pericardium.

Lymph Node map for Lung Cancer staging

CLINICAL FEATURESSymptoms of Central Tumors

Cough

Hemoptysis

Shortness of Breath

Wheezing and stridor

Postobstructive pneumonia

Symptoms of Peripheral Tumors

Pain

Shortness of breath

Pleural Effusion

Cough

Clinical findings suggestive of metastatic disease:

Symptoms elicited in history Constitutional : weight loss > 10 poundMusculoskeletal ; focal skeletal painNeurologic: headache , syncope , seizures , extremity weakness

Signs found on physical examination Lymphadenopathy(>1cm)Hoarsness , superior vena cava syndromeBone tendernessHepatomegaly (13> cm span)Focal neurologic signs , papilledemsSoft – tissue mass

Routine laboratory tests Hematocrit:<40% in men , <35% in womenElevated alkaline phosphatase , GGT ,SGOT and calcium levels

Syndromes/Symptoms secondary to regional metastases:

Esophageal compression dysphagia

Laryngeal nerve paralysis hoarseness

Symptomatic nerve paralysis Horner’s syndrome (enophthalmos, ptosis, miosis, and anhidrosis)

Cervical/thoracic nerve invasion Pancoast syndrome.

Lymphatic obstruction pleural effusion

Vascular obstruction SVC syndrome

Pericardial/cardiac extension effusion, tamponade

SUPERIOR VENA CAVA SYNDROME• Results from obstruction of blood flow to the heart from the head and

neck regions and upper extremities.

• It occurs as a consequence of compression of the superior vena cava, either from direct invasion by the primary tumor into the mediastinum or from lymphatic spread with enlarged right paratracheal lymph nodes.

• It is commonly caused by SCLC but can result from any centrally located tumor or mediastinal spread.

Features-1. Feeling of fullness in the head2. Dyspnea3. Cough4. Dilated neck veins5. Prominent venous pattern on the face and the chest6. Upper extremitt and facial edema7. Pappiledema8. Facial cyanosis9. Plethora10. Conjunctival edema(possibly)

PARANEOPLASTIC SYNDROMES

SIADH – Small cell –It results into HyponatremiaSymptoms include-Headache,Muscle cramps,Anorexia & Decreased

urine outputResolves within 1–4weeks of initiating chemotherapy.Demeclocycline is the agent of choice

Cushing Syndrome-ACTH-producing tumors – Small cell-Symptoms-Muscle weakness,weight loss,hypertension,hirsutism & osteoporosis.Hypokalemic alkalosis and hyperglycemia are present.It has worse prognosis

Hypercalcemia-Squamous cell –It is associated with secretion of

parathyroid hormone-related protein(PTHrp),calcitriol or other cytokines including osteoclast activating factors

Clinical symptoms include Anorexia,Nausea,Vomiting,Abdominal Pain,Lethargy,Constipation,Polyuria,Polydipsia AndThirst.

Late symptoms-Renal failure,confusion and coma.

Lambert-Eaton Myasthenic Syndrome(LEMS)It is characterized by muscle weakness of the limbs.Proximal muscles are affected associated with difficulty in climbing chairs and

rising from a sitting position.Chemotherapy is the initial treatment of choice.

Skeletal– Clubbing - 30% (usually NSCLCs) Hypertrophic primary osteoarthropathy - 1–10% (usually adenocarcinomas). Periostitis

Cutaneous manifestations – 1% - Dermatomyositis and - Acanthosis nigricans

Neurologic–Myopathic syndromes - 1% Myasthenic Eaton-Lambert syndrome and retinal blindness (SCLC). Peripheral neuropathies, Subacute cerebellar degeneration, Cortical degeneration, and Polymyositis

Hematologic manifestations – 1-8% -Migratory venous thrombophlebiti (Trousseau's syndrome), -Nonbacterial Thrombotic (marantic) endocarditis with arterial emboli, -Disseminated intravascular coagulation -Thrombotic disease complicating cancer is usually a poor prognostic sign.

LUNG CANCER METASTASIS• Adrenals - ~50% of cancers• Liver – 30-50%• Brain – 20%• Bone – 20%

DIAGNOSTIC WORK UP• Complete history• Complete physical examination

Chest-may show signs of-I. Partial or complete obstruction of airwaysII. PneumoniaIII. Pleural Effusion

Neck Examination-Signs of Supraclavicular lymphadenopathy

Abdominal examination-signs of hepatomegaly

Neurological examination-signs of Brain metastais

Haemogram• CBC-anemia due to metastatic disease

• LFT-May indicate Liver mets

• Increased ALP-May indicate Liver or Bone mets

• Increased Calcium ion-May indicate Bone mets or Paraneoplastic syndrome

RADIOLOGIC EXAMINATIONS• Chest Xray-initial imaging modality.• Current Xray should be compared with previous ones to determine if a lesion is-• New• Enlarging or • Stable

• CT Scan-• CECT Chest + Upper Abdomen should be done so that Liver and Adrenals can be

visualized

• In a patient with known lung cancer a lymph node is considered suspicious if it measures >1cm in diameter on its short axis.

• It can establish T stage by-I. Determining tumor sizeII. Presence of separate tumor nodulesIII. Presence of atelectasisIV. Post obstructive pneumoniaV. Invasion of adjacent structuresVI. Proximal extent of the tumor

• PET or PET-CT SCAN• It has become standard in the staging work up of lung cancer patients.

• The biggest advantage is the identification of suspicious lymph nodes or distant metastasis.

• Kaeff et al prospectively evaluated the utility of PET-• They found that PET correctly upstaged 26% patients• and downstaged 10-16 patients.

• Additionally PET can detect malignant disease in lymph nodes of normal size.• PET-CT is superior to CT or PET alone and can detect malignancies in tumors as

small as 0.5cm.

• Novel tracers-• FDG• FMISO(18F-fluoromisonidazole)-For tumor Hypoxia• FLT(18F-fluorothymidine)-For tumor proliferation• 11C-methionine and 11C-tyrosine-For amino acid metabolism.

• Sputum Cytology-Sensitivity is 65%.

• Percutaneous Fine Needle Aspiration(FNA)-• CT guided FNA done in lesions which cannot be reached by Bronchoscopy.

Overall diagnostic yield is 80%.

• Bronchoscopy-• FOB is done and cytologic brushings,biopsies can be taken.

Biopsy - confirm the cancer and determine the type

Bronchoscopy CT guided biopsy

• Endoscopic FNA-• Endobronchial USG guided transbronchial needle aspiration(EBUS-TBNA) can be

done for ultrasound suspicious lymph nodes-Paratracheal-Level 2 & 4Subcarinal-Level 7Hilar lymph node stations-level 10

• Thoracocentesis-• If on multiple taps of pleural fluid is consistently bloody or exudative ,it should be

considered malignant.

• Thoracoscopy• Video assisted thoracoscopy(VAT) is used for-

I. DiagnosisII. StagingIII. Resection of lung cancer

• Peripheral nodules can be easily seen and excised.

• It can also be used to reach mediastinal nodes not accessible by standard mediastinoscopy,EBUS-TBNA or EUS-FNA techniques.

AJCC STAGING

PATHOLOGIC CLASSIFICATION• 1.Preinvasive lesions

• Squamous dysplasia/carcinoma in situ• Atypical adenomatous hyperplasia• Adenocarcinoma in situ(non mucinous,mucinous or mixed nonmucinous/mucinous)• Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

• 2.Squamous cell carcinoma• Variants

• Papillary• Clear cell• Small cell• Basoloid

• 3.Small cell carcinoma• Combined small cell carcinoma

• 4.Adenocarcinoma• Minimally invasive adenocarcinoma(<3cm lepidic predominant tumor with <5mm

invasion)• Non mucinous,mucinous or mixed nonmucinous/mucinous

• Invasive adenocarcinoma• Lepidic predominant (formerly nonmucinous BAC pattern,with >5mm invasion)• Acinar predominant• Papillary predominant• Micropapillary predominant• Solid predominant

• Variants of invasive adenocarcinoma• Invasive mucinous adenocarcinoma(formerly mucinous BAC)• Colloid• Fetal(low and high grade)• Enteric

• 5.Large cell carcinoma• Variants• Large cell neuroendocrine carcinoma• Combined large cell neuroendocrine carcinoma

• Basaloid carcinoma• Lymphoepithelioma-like carcinoma• Clear cell carcinoma• Large cell carcinoma with rhabdoid phenotype

• 6.Adenosquamous carcinoma• 7.Sarcomatoid carcinoma• Pleomorphic carcinoma• Spindle cell carcinoma• Giant cell carcinoma• Carcinosarcoma• Pulmonary blastoma• Other

• 8.Carcinoid tumour• Typical carcinoid• Atypical carcinoid

• 9.Carcinomas of salivary gland type• Mucoepidermoid carcinoma• Adenoid cystic carcinoma• Epimyoepithelial carcinoma

These four histologies account for approximately 90% of all epithelial lung cancers.

1.Small Cell Lung Cancer (SCLC)

2.Adenocarcinoma

3.Squamous Cell Carcinoma

4.Large Cell Carcinoma

Non Small Cell Lung Cancer(NSCLC)

Adeno

Squamous

Large

Small

Epithelial cell lung cancers

:Harrison's Principles of Internal Medicine, 18e

Squamous

Adeno

Large

Others

WESTERN COUNTRIES INDIA-1986-2001

:IACM Journal April-June 2012

LUNG CANCER IN INDIANon-small-cell lung cancer constitutes 75 - 80% of lung cancers. More than 70 % of them are in Stages III and IV, thus curative surgery can not be done in these cases.

Small-cell lung carcinoma constitute 20% of all lung cancers . Extensive stage in 70% of patients at the time of diagnosis.

While in many Western countries adenocarcinoma has become the commonest lung cancer.

In India it is still squamous cell carcinoma in both males and females

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